The accurate and rapid transfer of fluids is an integral part of nearly every biochemical reaction, assay or diagnostic test. While fluid transfer technology using disposable polymer pipette tips is well developed for volumes above one microliter, manipulating the smaller volumes required for high throughput screening using syringe-solenoid, inkjet or acoustic dispensers is very expensive and slow. Using silicon micromachining techniques, our Phase I effort has produced a new silicon tool set that provides previously inaccessible transfer volumes over many orders of magnitude (from ~50 pL to 5 5L), a price far below competing technologies, very high accuracy and a transfer rate many times greater than any other fluid transfer technology. This new Fluid Transfer Pin (FTP) technology derives from the extremely high accuracy inherent in the micromachining technology used to prepare the silicon transfer pins and collimators which can align the pins to an accuracy of a few microns within the printhead. The key to the accuracy and dynamic range of the fluid volume transferred is the concept of the silicon "TwinPin" which was invented during the Phase I effort. The uptake volume is held between two silicon pins that are held exactly parallel to one another by the micromachined silicon collimators within the printhead. Altering the distance between the two flat parallel pin shafts by changing the silicon collimators varies the volume of fluid transferred between 50 pL and several 5L. Furthermore, unlike any other type of small volume fluid dispensing device, the TwinPins can perform both wet transfers (the imbibed sample is submersed into a liquid- filled destination microtiter plate well and the FTP's fluid allowed to diffuse into the well fluid) or dry transfers (touching a dry well bottom, in a fashion similar to microarray printing, with the pin tip to transfer a small droplet of liquid into the well). By virtue of the 384-element printhead, samples may be dispensed at a rate 15 times faster than an acoustic dispenser at <1/10th the cost. Furthermore, the use of the TwinPins to print protein and DNA microarrays allows for the first time to print any spot size between 505 and >10005 by using the same pin set and simply changing the collimator. Since most protein microarrays arrays with spots larger than ~6005 are printed with solid pins, which require washing and refilling after the deposition of each spot, use of the TwinPins for the deposition of large spots will allow hundreds of spots to be deposited without revisiting the source plate thereby decreasing the time and cost for any microarray production. In the Phase II effort the FTP technology will be evaluated in the laboratories of Prof. Joseph DeRisi at UCSF and with Dr. John Coller, Director of the Stanford Functional Genomics Facility at Stanford University and their feedback incorporated into the final designs. PUBLIC HEALTH RELEVANCE: Silicon fluid transfer pin (FTP) tools represent a technological advance that enables access to accurate and rapid extremely-low-volume transfer at a very low cost as compared to current technologies that achieve the same result. This will allow for high- throughput research to advance at all industry and academic levels without the limitations of high cost of overly technical equipment that is often difficult to setup and use. In addition to performing accurate and precise nanoliter volume transfer, the function of silicon FTPs can be expanded by applying special coatings to the pin surface from which more complex biological operations can be performed.